SLOW AND INCOMPLETE INACTIVATIONS OF VOLTAGE-GATED CHANNELS DOMINATE ENCODING IN SYNTHETIC NEURONS

Electrically excitable channels were expressed in Chinese hamster ovar y cells using a vaccinia virus vector system. In cells expressing rat brain IIA Na+ channels only, brief pulses (< 1 ms) of depolarizing cur rent resulted in action potentials with a prolonged (0.5-3 s) depolari zing plateau; this plateau was caused by slow and incomplete Na+ chann el inactivation. In cells expressing both Na+ and Drosophila Shaker H4 transient K+ channels, there were neuron-like action potentials. In c ells with appropriate Na+/K+ current ratios, maintaining stimulation p roduced repetitive firing over a 10-fold range of frequencies but even tually led to ''lockup'' of the potential at a positive value after se veral seconds of stimulation. The latter effect was due primarily to s low inactivation of the K+ currents. Numerical simulations of modified Hodgkin-Huxley equations describing these currents, using parameters from voltage-clamp kinetics studied in the same cells, accounted for m ost features of the voltage trajectories. The present study shows that insights into the mechanisms for generating action potentials and tra ins of action potentials in real excitable cells can be obtained from the analysis of synthetic excitable cells that express a controlled re pertoire of ion channels.